Rapid, reliable, and sensitive assay systems for testing antiviral activity of potential drugs are essential for the development of antiviral therapy of AIDS. Multiple in vitro assay systems have now been available and these assay systems should further accelerate the identification of new antiretroviral agents. However, a number of variables or factors influence the results of the in vitro antiviral testing. Antiviral data can greatly vary depending on the target cells employed. Viral doses, viral strains, time of drug addition, duration of culture, and endpoints used can also significantly influence the antiviral data. Human peripheral blood mononuclear cells (PBM) have been frequently used as target cells following stimulation with phytohemagglutinin (PHA) for the study of activity of various drugs against HIV. PHA-stimulated PBM (PHA-PBM) may provide a milieu close to the in vivo situation and therefore may serve as one of the most suitable target cells for antiviral testing. However, it is as yet poorly understood whether the sensitivity of HIV-1 to drugs as assessed in PHA-PBM correlates with the virus-drug interactions in patients with AIDS.